Title:The Role of the Cannabinoid System in Opioid Analgesia and Tolerance
VOLUME: 20 ISSUE: 10
Author(s):Ercan Ozdemir*
Affiliation:Department of Physiology, School of Medicine, Cumhuriyet University, 58140 Sivas
Keywords:Cannabinoids, cannabinoid receptors, cannabinoid analgesia, opioid analgesia, opioid tolerance, analgesic.
Abstract:Opioid receptor agonist drugs, such as morphine, are very effective for treating chronic and
severe pain; but, tolerance can develop with long-term use. Although there is a lot of information about
the pathophysiological mechanisms of opioid tolerance, it is still not fully clarified. Suggested
mechanisms for opioid tolerance include opioid receptor desensitisation, reduction of sensitivity
G-proteins, activation of Mitogen-Activated Protein Kinase (MAPK), altered intracellular signaling
pathway including nitric oxide, and activation of mammalian Target of Rapamycin (mTOR). One way
to reduce opioid tolerance and increase the analgesic potential is to use low doses. Combination of
cannabinoids with opioids has been shown to manifest the reduction of the opioid dose. Experimental
studies revealed an interaction of the endocannabinoid system and opioid antinociception. Cannabinoid
and opioid receptor systems use common pathways in the formation of analgesic effect and
demonstrate their activity via G Protein Coupled Receptors (GPCR). Cannabinoid drugs modulate
opioid analgesic activity at a number of distinct levels within the cell, ranging from direct receptor
associations to post-receptor interactions through shared signal transduction pathways. This review
summarizes the data indicating that with combining cannabinoids and opioids drugs may be able to
produce long-term analgesic effects, while preventing the opioid analgesic tolerance.